Background/Aims: Iron accumulation in vital organs such as heart and liver is a major pathology in β-thalassaemia. It may also affect mature RBCs and developing erythroid precursors. The cellular damage is mainly caused by the labile iron pool (LIP) and is mediated by reactive oxygen species (ROS). We have previously shown that thalassaemic RBCs and their precursors have more LIP and ROS than their normal counterparts. We now report the effect of clinically relevant iron chelators on these parameters. Methods: RBCs, reticulocytes and cultured erythroid precursors derived from patients with β-thalassaemia were studied for LIP and oxidative stress parameters by flow-cytometry. Results: In vitro treatment with deferiprone, deferasirox and deferoxamine reduced the cytosolic LIP in RBCs and reticulocytes, and both the cytosolic and mitochondrial LIP in cultured erythroid precursors. This was associated with reduced oxidative stress (ROS and external phosphatidylserine). While the effect of deferiprone and deferasirox was fast (within 10 min), deferoxamine affected these parameters after 24 h, suggesting a slower rate of entry. Conclusion: The chelators studied reduce the LIP and the oxidative status of thalassaemic RBC and their precursors. Whether these effects directly improve ineffective erythropoiesis and RBC survival remains to be shown.

Keywords:
Erythropoiesis, Flow cytometry, Thalassaemia, Iron, Red blood cells
© 2009 S. Karger AG, Basel
2009
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